TY - JOUR A1 - Löb, Sanja A1 - Linsmeier, Eva A1 - Herbert, Saskia-Laureen A1 - Schlaiß, Tanja A1 - Kiesel, Matthias A1 - Wischhusen, Jörg A1 - Salmen, Jessica A1 - Kranke, Peter A1 - Quenzer, Anne A1 - Kurz, Florian A1 - Weiss, Claire A1 - Gerhard-Hartmann, Elena A1 - Wöckel, Achim A1 - Diessner, Joachim T1 - Prognostic effect of HER2 evolution from primary breast cancer to breast cancer metastases JF - Journal of Cancer Research and Clinical Oncology N2 - Purpose Therapeutic options for breast cancer (BC) treatment are constantly evolving. The Human Epidermal Growth Factor 2 (HER2)-low BC entity is a new subgroup, representing about 55% of all BC patients. New antibody–drug conjugates demonstrated promising results for this BC subgroup. Currently, there is limited information about the conversion of HER2 subtypes between primary tumor and recurrent disease. Methods This retrospective study included women with BC at the University Medical Centre Wuerzburg from 1998 to 2021. Data were retrieved from patients' records. HER2 evolution from primary diagnosis to the first relapse and the development of secondary metastases was investigated. Results In the HR-positive subgroup without HER2 overexpression, HER2-low expression in primary BC was 56.7 vs. 14.6% in the triple-negative subgroup (p < 0.000). In the cohort of the first relapse, HER2-low represented 64.1% of HR-positive vs. 48.2% of the triple-negative cohort (p = 0.03). In patients with secondary metastases, HER2-low was 75.6% vs. 50% in the triple negative subgroup (p = 0.10). The subgroup of HER2-positive breast cancer patients numerically increased in the course of disease; the HER2-negative overall cohort decreased. A loss of HER2 expression from primary BC to the first relapse correlated with a better OS (p = 0.018). No clinicopathological or therapeutic features could be identified as potential risk factors for HER2 conversion. Conclusion HER2 expression is rising during the progression of BC disease. In view of upcoming therapeutical options, the re-analysis of newly developed metastasis will become increasingly important. KW - breast cancer KW - HER2 conversion KW - HER2-low KW - trastuzumab deruxtecan KW - HER2 targeted therapy KW - trastuzumab Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324068 VL - 149 IS - 8 ER - TY - THES A1 - Sun, Aili T1 - Effect of Tjap1 knock-down on blood-brain barrier properties under normal and hypoxic conditions T1 - Auswirkung des Tjap1-Knockdowns auf die Eigenschaften der Blut-Hirn-Schranke unter normalen und hypoxischen Bedingungen N2 - Stroke is one of the leading causes of mortality and disability worldwide. The blood-brain barrier (BBB) plays an important role in maintaining brain homeostasis by tightly regulating the exchange of substances between circulating blood and brain parenchyma. BBB disruption is a common pathologic feature of stroke and traumatic brain injury. Understanding the cellular and molecular events that affect the BBB after ischaemic brain injury is important to improve patient prognosis. We have previously shown that microRNA-212/132 is elevated in hypoxic brain microvascular endothelial cells and acts through suppressing the expression of direct microRNA-212/132 target genes with function at the BBB: claudin-1, junctional adhesion molecule 3 (Jam3) and tight-junction associated protein 1 (Tjap1). While the role of claudin-1 and Jam3 at the BBB is well known, the role of Tjap1 is still unclear. The aim of this work was therefore to characterize the role of Tjap1 in brain endothelial cells using a knock-down (KD) approach in established murine in vitro BBB models cEND and cerebEND. Tjap1 KD was established by stable transfection of a plasmid expressing shRNA against Tjap1. The successful downregulation of Tjap1 mRNA and protein was demonstrated by qPCR and Western blot. Tjap1 KD resulted in impaired barrier properties of endothelial cells as shown by lower TEER values and higher paracellular permeability. Interestingly, the Tjap1 KD cells showed lower cell viability and proliferation but migrated faster in a wound healing assay. In the tube formation assay, Tjap1 KD cell lines showed a lower angiogenic potential due to a significantly lower tube length and number as well as a lower amount of branching points in formed capillaries. Tjap1 KD cells showed changes in gene and protein expression. The TJ proteins claudin-5, Jam3 and ZO-1 were significantly increased in Tjap1 KD cell lines, while occludin was strongly decreased. In addition, efflux pump P-glycoprotein was downregulated in Tjap1 KD cells. Oxygen-glucose deprivation (OGD) is a method to mimic stroke in vitro. Brain endothelial cell lines treated with OGD showed lower barrier properties compared to cells cultured under normal condition. These effects were more severe in Tjap1 KD cells, indicating active Tjap1 involvement in the OGD response in brain microvascular endothelial cells. We thus have shown that Tjap1 contributes to a tight barrier of the BBB, regulates cell viability and proliferation of endothelial cells, suppresses their migration and promotes new vessel formation. This means that Tjap1 function is important for mature BBB structure in health and disease. N2 - Schlaganfall ist weltweit eine der häufigsten Ursachen für Mortalität und Behinderung. Die Blut-Hirn-Schranke (BHS) spielt eine wichtige Rolle bei der Aufrechterhaltung der Gehirnhomöostase, indem sie den Stoffaustausch zwischen dem zirkulierenden Blut und dem Gehirnparenchym streng reguliert. Eine Störung der BHS ist ein gemeinsames pathologisches Merkmal von Schlaganfällen und traumatischen Hirnverletzungen. Um die Prognose der Patientinnen und Patienten zu verbessern, ist es wichtig, die zellulären und molekularen Ereignisse zu verstehen, die sich nach einer ischämischen Hirnverletzung auf die BHS auswirken. Wir haben zuvor gezeigt, dass microRNA-212/132 in hypoxischen mikrovaskulären Endothelzellen erhöht ist und durch die Unterdrückung der Expression direkter Zielgene mit Funktion and der BHS wirkt. Zu den Zielgenen von microRNA-212/132 gehören: Claudin-1, Junctional Adhesion Molecule 3 (Jam3) und Tight Junction Associated Protein 1 (Tjap1). Während die Rolle von Caludin-1 und Jam3 and der BHS gut bekannt ist, ist die Rolle von Tjap1 noch unklar. Ziel dieser Arbeit war es daher, die Rolle von Tjap1 in Endothelzellen mithilfe eines Knock-down (KD)-Ansatzes in etablierten murinen In-vitro-BHS-Modellen zu charakterisieren. Tjap1-KD wurde durch stabile Transfektion eines Plasmids etabliert, das shRNA gegen Tjap1 exprimiert. Die erfolgreiche Herunterregulierung von Tjap1-mRNA und -Protein wurde durch qPCR und Western Blot nachgewiesen. Tjap1-KD führte zu einer Beeinträchtigung der Barriereeigenschaften von Endothelzellen, was sich in niedrigeren TEER-Werten und einer höheren parazellulären Permeabilität wiederspiegelte. Interessanterweise zeigten die Tjap1-KD-Zellen in einem Wundheilungstest eine geringere Zelllebensfähigkeit und Proliferation, wanderten jedoch schneller. Im tube formation assay zeigten Tjap1-KD-Zelllinien ein geringeres Angiogenese-Potential durch eine signifikant geringere Anzahl der gebildeten Kapillaren. Tjap-1-KD-Zellen zeigten Veränderungen in der Gen- und Proteinexpression. Die TJ-Proteinen Claudin-5, Jam3 und ZO-1 waren in Tjap1-KD-Zelllinien signifikant erhöht, während Occludin stark verringert war. Darüber hinaus wurde P-Glykoprotein in Tjap1-KD-Zellen herunterreguliert. Sauerstoff-Glukose-Entzug (eng. oxygen/glucose-deprivation, OGD) ist eine Methode zur Nachahmung eines Schlaganfall in vitro. Mit OGD behandelte Endothelzelllinien zeigten im Vergleich zu unter normalen Bedingungen kultivierten Zellen geringere Barriereeigenschaften. Diese Effekte waren in Tjap1-KD-Zellen schwerwiegender, was auf eine aktive Beteiligung von Tjap1 an der OGD-Antwort in Endothelzellen hinweist. Wir haben gezeigt, dass Tjap1 zu einer dichten Barriere der BHS beiträgt, die Zellviabilität und die Proliferation von Endothelzellen reguliert, deren Migration unterdrückt und die Bildung neuer Gefäße fördert. Dies bedeutet, dass die Tjap1-Funktion für die reife BHS-Struktur unter physiologischen und pathophysiologischen Bedingungen wichtig ist. KW - Schlaganfall KW - Blut-Hirn-Schranke KW - blood-brain barrier KW - Tjap1 KW - oxygen/glucose deprivation KW - stroke Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-346450 ER - TY - JOUR A1 - Henckert, David A1 - Malorgio, Amos A1 - Schweiger, Giovanna A1 - Raimann, Florian J. A1 - Piekarski, Florian A1 - Zacharowski, Kai A1 - Hottenrott, Sebastian A1 - Meybohm, Patrick A1 - Tscholl, David W. A1 - Spahn, Donat R. A1 - Roche, Tadzio R. T1 - Attitudes of anesthesiologists toward artificial intelligence in anesthesia: a multicenter, mixed qualitative–quantitative study JF - Journal of Clinical Medicine N2 - Artificial intelligence (AI) is predicted to play an increasingly important role in perioperative medicine in the very near future. However, little is known about what anesthesiologists know and think about AI in this context. This is important because the successful introduction of new technologies depends on the understanding and cooperation of end users. We sought to investigate how much anesthesiologists know about AI and what they think about the introduction of AI-based technologies into the clinical setting. In order to better understand what anesthesiologists think of AI, we recruited 21 anesthesiologists from 2 university hospitals for face-to-face structured interviews. The interview transcripts were subdivided sentence-by-sentence into discrete statements, and statements were then grouped into key themes. Subsequently, a survey of closed questions based on these themes was sent to 70 anesthesiologists from 3 university hospitals for rating. In the interviews, the base level of knowledge of AI was good at 86 of 90 statements (96%), although awareness of the potential applications of AI in anesthesia was poor at only 7 of 42 statements (17%). Regarding the implementation of AI in anesthesia, statements were split roughly evenly between pros (46 of 105, 44%) and cons (59 of 105, 56%). Interviewees considered that AI could usefully be used in diverse tasks such as risk stratification, the prediction of vital sign changes, or as a treatment guide. The validity of these themes was probed in a follow-up survey of 70 anesthesiologists with a response rate of 70%, which confirmed an overall positive view of AI in this group. Anesthesiologists hold a range of opinions, both positive and negative, regarding the application of AI in their field of work. Survey-based studies do not always uncover the full breadth of nuance of opinion amongst clinicians. Engagement with specific concerns, both technical and ethical, will prove important as this technology moves from research to the clinic. KW - artificial intelligence KW - machine learning KW - anesthesia KW - anesthesiology KW - qualitative research KW - clinical decision support Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311189 SN - 2077-0383 VL - 12 IS - 6 ER - TY - JOUR A1 - Hohm, Anna A1 - Happel, Oliver A1 - Hurtienne, Jörn A1 - Grundgeiger, Tobias T1 - User experience in safety–critical domains: a survey on motivational orientations and psychological need satisfaction in acute care JF - Cognition, Technology & Work N2 - The relevance of user experience in safety–critical domains has been questioned and lacks empirical investigation. Based on previous studies examining user experience in consumer technology, we conducted an online survey on positive experiences with interactive technology in acute care. The participants of the study consisted of anaesthesiologists, nurses, and paramedics (N = 55) from three German cities. We report qualitative and quantitative data examining (1) the relevance and notion of user experience, (2) motivational orientations and psychological need satisfaction, and (3) potential correlates of hedonic, eudaimonic, and extrinsic motivations such as affect or meaning. Our findings reveal that eudaimonia was the most salient aspect in these experiences and that the relevance of psychological needs is differently ranked than in experiences with interactive consumer technology. We conclude that user experience should be considered in safety–critical domains, but research needs to develop further tools and methods to address the domain-specific requirements. KW - user experience KW - healthcare KW - eudaimonia KW - hedonia KW - need satisfaction KW - meaning Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324486 SN - 1435-5558 VL - 24 IS - 2 ER - TY - JOUR A1 - Schweiger, Giovanna A1 - Malorgio, Amos A1 - Henckert, David A1 - Braun, Julia A1 - Meybohm, Patrick A1 - Hottenrott, Sebastian A1 - Froehlich, Corinna A1 - Zacharowski, Kai A1 - Raimann, Florian J. A1 - Piekarski, Florian A1 - Noethiger, Christoph B. A1 - Spahn, Donat R. A1 - Tscholl, David W. A1 - Roche, Tadzio R. T1 - Visual Blood, a 3D animated computer model to optimize the interpretation of blood gas analysis JF - Bioengineering N2 - Acid–base homeostasis is crucial for all physiological processes in the body and is evaluated using arterial blood gas (ABG) analysis. Screens or printouts of ABG results require the interpretation of many textual elements and numbers, which may delay intuitive comprehension. To optimise the presentation of the results for the specific strengths of human perception, we developed Visual Blood, an animated virtual model of ABG results. In this study, we compared its performance with a conventional result printout. Seventy physicians from three European university hospitals participated in a computer-based simulation study. Initially, after an educational video, we tested the participants’ ability to assign individual Visual Blood visualisations to their corresponding ABG parameters. As the primary outcome, we tested caregivers’ ability to correctly diagnose simulated clinical ABG scenarios with Visual Blood or conventional ABG printouts. For user feedback, participants rated their agreement with statements at the end of the study. Physicians correctly assigned 90% of the individual Visual Blood visualisations. Regarding the primary outcome, the participants made the correct diagnosis 86% of the time when using Visual Blood, compared to 68% when using the conventional ABG printout. A mixed logistic regression model showed an odds ratio for correct diagnosis of 3.4 (95%CI 2.00–5.79, p < 0.001) and an odds ratio for perceived diagnostic confidence of 1.88 (95%CI 1.67–2.11, p < 0.001) in favour of Visual Blood. A linear mixed model showed a coefficient for perceived workload of −3.2 (95%CI −3.77 to −2.64) in favour of Visual Blood. Fifty-one of seventy (73%) participants agreed or strongly agreed that Visual Blood was easy to use, and fifty-five of seventy (79%) agreed that it was fun to use. In conclusion, Visual Blood improved physicians’ ability to diagnose ABG results. It also increased perceived diagnostic confidence and reduced perceived workload. This study adds to the growing body of research showing that decision-support tools developed around human cognitive abilities can streamline caregivers’ decision-making and may improve patient care. KW - blood gas analysis KW - medical devices KW - point-of-care-testing KW - situational awareness KW - technology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304150 SN - 2306-5354 VL - 10 IS - 3 ER - TY - JOUR A1 - Bergauer, Lisa A1 - Akbas, Samira A1 - Braun, Julia A1 - Ganter, Michael T. A1 - Meybohm, Patrick A1 - Hottenrott, Sebastian A1 - Zacharowski, Kai A1 - Raimann, Florian J. A1 - Rivas, Eva A1 - López-Baamonde, Manuel A1 - Spahn, Donat R. A1 - Noethiger, Christoph B. A1 - Tscholl, David W. A1 - Roche, Tadzio R. T1 - Visual Blood, visualisation of blood gas analysis in virtual reality, leads to more correct diagnoses: a computer-based, multicentre, simulation study JF - Bioengineering N2 - Interpreting blood gas analysis results can be challenging for the clinician, especially in stressful situations under time pressure. To foster fast and correct interpretation of blood gas results, we developed Visual Blood. This computer-based, multicentre, noninferiority study compared Visual Blood and conventional arterial blood gas (ABG) printouts. We presented six scenarios to anaesthesiologists, once with Visual Blood and once with the conventional ABG printout. The primary outcome was ABG parameter perception. The secondary outcomes included correct clinical diagnoses, perceived diagnostic confidence, and perceived workload. To analyse the results, we used mixed models and matched odds ratios. Analysing 300 within-subject cases, we showed noninferiority of Visual Blood compared to ABG printouts concerning the rate of correctly perceived ABG parameters (rate ratio, 0.96; 95% CI, 0.92–1.00; p = 0.06). Additionally, the study revealed two times higher odds of making the correct clinical diagnosis using Visual Blood (OR, 2.16; 95% CI, 1.42–3.29; p < 0.001) than using ABG printouts. There was no or, respectively, weak evidence for a difference in diagnostic confidence (OR, 0.84; 95% CI, 0.58–1.21; p = 0.34) and perceived workload (Coefficient, 2.44; 95% CI, −0.09–4.98; p = 0.06). This study showed that participants did not perceive the ABG parameters better, but using Visual Blood resulted in more correct clinical diagnoses than using conventional ABG printouts. This suggests that Visual Blood allows for a higher level of situation awareness beyond individual parameters’ perception. However, the study also highlighted the limitations of today’s virtual reality headsets and Visual Blood. KW - virtual reality KW - blood gas analysis KW - data display KW - point-of-care KW - situation awareness KW - user-centred design KW - diagnostic correctness Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-310979 SN - 2306-5354 VL - 10 IS - 3 ER - TY - JOUR A1 - Hinkelbein, Jochen A1 - Iovino, Ivan A1 - De Robertis, Edoardo A1 - Kranke, Peter T1 - Outcomes in video laryngoscopy studies from 2007 to 2017: systematic review and analysis of primary and secondary endpoints for a core set of outcomes in video laryngoscopy research JF - BMC Anesthesiology N2 - Background Airway management is crucial and, probably, even the most important key competence in anaesthesiology, which directly influences patient safety and outcome. However, high-quality research is rarely published and studies usually have different primary or secondary endpoints which impedes clear unbiased comparisons between studies. The aim of the present study was to gather and analyse primary and secondary endpoints in video laryngoscopy studies being published over the last ten years and to create a core set of uniform or homogeneous outcomes (COS). Methods Retrospective analysis. Data were identified by using MEDLINE® database and the terms “video laryngoscopy” and “video laryngoscope” limited to the years 2007 to 2017. A total of 3351 studies were identified by the applied search strategy in PubMed. Papers were screened by two anaesthesiologists independently to identify study endpoints. The DELPHI method was used for consensus finding. Results In the 372 studies analysed and included, 49 different outcome categories/columns were reported. The items “time to intubation” (65.86%), “laryngeal view grade” (44.89%), “successful intubation rate” (36.56%), “number of intubation attempts” (23.39%), “complications” (21.24%), and “successful first-pass intubation rate” (19.09%) were reported most frequently. A total of 19 specific parameters is recommended. Conclusions In recent video laryngoscopy studies, many different and inhomogeneous parameters were used as outcome descriptors/endpoints. Based on these findings, we recommend that 19 specific parameters (e.g., “time to intubation” (inserting the laryngoscope to first ventilation), “laryngeal view grade” (C&L and POGO), “successful intubation rate”, etc.) should be used in coming research to facilitate future comparisons of video laryngoscopy studies. KW - airway management KW - video laryngoscopy KW - primary outcome KW - primary endpoint Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-320747 VL - 19 ER - TY - JOUR A1 - Lambertini, Alessandro A1 - Hartrampf, Philipp E. A1 - Higuchi, Takahiro A1 - Serfling, Sebastian E. A1 - Meybohm, Patrick A1 - Schirbel, Andreas A1 - Buck, Andreas K. A1 - Werner, Rudolf A. T1 - CXCR4-targeted molecular imaging after severe SARS-Cov-2 infection JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - No abstract available. KW - CXCR4-targeting KW - SARS-CoV-2 KW - COVID-19 KW - molecular imaging Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324619 VL - 50 IS - 1 ER - TY - JOUR A1 - Wilhelms, Benedikt A1 - Broscheit, Jens A1 - Shityakov, Sergey T1 - Chemical analysis and molecular modelling of cyclodextrin-formulated propofol and its sodium salt to improve drug solubility, stability and pharmacokinetics (cytogenotoxicity) JF - Pharmaceuticals N2 - Propofol is a widely used general anesthetic in clinical practice, but its use is limited by its water-insoluble nature and associated pharmacokinetic and pharmacodynamic limitations. Therefore, researchers have been searching for alternative formulations to lipid emulsion to address the remaining side effects. In this study, novel formulations for propofol and its sodium salt Na-propofolat were designed and tested using the amphiphilic cyclodextrin (CD) derivative hydroxypropyl-β-cyclodextrin (HPβCD). The study found that spectroscopic and calorimetric measurements suggested complex formation between propofol/Na-propofolate and HPβCD, which was confirmed by the absence of an evaporation peak and different glass transition temperatures. Moreover, the formulated compounds showed no cytotoxicity and genotoxicity compared to the reference. The molecular modeling simulations based on molecular docking predicted a higher affinity for propofol/HPβCD than for Na-propofolate/HPβCD, as the former complex was more stable. This finding was further confirmed by high-performance liquid chromatography. In conclusion, the CD-based formulations of propofol and its sodium salt may be a promising option and a plausible alternative to conventional lipid emulsions. KW - propofol KW - anaesthesiology KW - HPβCD KW - \(^1\)H-NMR spectroscopy KW - calorimetry KW - molecular modelling KW - cytotoxicity KW - genotoxicity Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313705 SN - 1424-8247 VL - 16 IS - 5 ER - TY - JOUR A1 - Holzmann-Littig, Christopher A1 - Stadler, David A1 - Popp, Maria A1 - Kranke, Peter A1 - Fichtner, Falk A1 - Schmaderer, Christoph A1 - Renders, Lutz A1 - Braunisch, Matthias Christoph A1 - Assali, Tarek A1 - Platen, Louise A1 - Wijnen-Meijer, Marjo A1 - Lühnen, Julia A1 - Steckelberg, Anke A1 - Pfadenhauer, Lisa A1 - Haller, Bernhard A1 - Fuetterer, Cornelia A1 - Seeber, Christian A1 - Schaaf, Christian T1 - Locating medical information during an infodemic: information seeking behavior and strategies of health-care workers in Germany JF - Healthcare N2 - Background: The COVID-19 pandemic has led to a flood of — often contradictory — evidence. HCWs had to develop strategies to locate information that supported their work. We investigated the information-seeking of different HCW groups in Germany. Methods: In December 2020, we conducted online surveys on COVID-19 information sources, strategies, assigned trustworthiness, and barriers — and in February 2021, on COVID-19 vaccination information sources. Results were analyzed descriptively; group comparisons were performed using χ\(^2\)-tests. Results: For general COVID-19-related medical information (413 participants), non-physicians most often selected official websites (57%), TV (57%), and e-mail/newsletters (46%) as preferred information sources — physicians chose official websites (63%), e-mail/newsletters (56%), and professional journals (55%). Non-physician HCWs used Facebook/YouTube more frequently. The main barriers were insufficient time and access issues. Non-physicians chose abstracts (66%), videos (45%), and webinars (40%) as preferred information strategy; physicians: overviews with algorithms (66%), abstracts (62%), webinars (48%). Information seeking on COVID-19 vaccination (2700 participants) was quite similar, however, with newspapers being more often used by non-physicians (63%) vs. physician HCWs (70%). Conclusion: Non-physician HCWs more often consulted public information sources. Employers/institutions should ensure the supply of professional, targeted COVID-19 information for different HCW groups. KW - COVID-19 KW - infodemic KW - health-care workers KW - HCW KW - information strategies KW - emergency information Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319306 SN - 2227-9032 VL - 11 IS - 11 ER -